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PubMed1982

Association of a better kidney graft survival with the presence of circulating immune complexes before transplantation.

The presence of circulating immune complexes was investigated using the C1q-binding assay before and after kidney transplantation in 48 patients with renal failure. Circulating immune complexes were found in 54% of the patients. The presence of circulating immune complexes prior to grafting was associated with a better renal graft survival. Median survival time of grafts in patients with circulating immune complexes was more than 18 months as compared with 21/2 months in patients without such complexes. The incidence of circulating immune complexes in patients before transplant could not be related to the renal disease, viral infections, blood transfusions, or serum levels of lymphocytotoxic antibodies, IgG, or IgM.

Antigen-Antibody Complex↗
PubMedDate not supplied

The pathogenesis of arthritis in Lyme disease: humoral immune responses and the role of intra-articular immune complexes.

We studied 78 patients with Lyme disease to determine how immune complexes and autoantibodies are related to the development of chronic Lyme arthritis. Circulating C1q binding material was found in nearly all patients at onset of erythema chronicum migrans, the skin lesion that marks the onset of infection with the causative spirochete. In patients with only subsequent arthritis this material tended to localize to joints where it gradually increased in concentrations with greater duration of joint inflammation. In joints, its concentration correlated positively with the number of synovial fluid polymorphonuclear leukocytes. Despite the prolonged presence of putative immune complexes, rheumatoid factors could not be demonstrated. These observations suggest that phlogistic immune complexes based on spirochete antigens form locally within joints during chronic Lyme arthritis.

Antigen-Antibody Complex↗
PubMed2001

Increased level of soluble HLA class I antigens in systemic lupus erythematosus: correlation with anti-DNA antibodies and leukopenia.

The concentration of soluble HLA class I (sHLA-I) was measured by ELISA in serum samples from 30 well-characterised SLE patients at high and low disease activity states and from 100 healthy controls. HLA-A allotypes in the patients were analysed by a PCR-based typing technique. A higher level of sHLA-I was found in SLE patient sera both at high and low disease activity than in controls (P< 0.001). The sHLA-I level was further increased during active disease (P< 0.01). Concentrations of sHLA-I correlated with anti-dsDNA antibodies at high disease activity, but not with disease activity as analysed by a modified SLEDAI. Numbers of leukocytes and lymphocytes, as well as levels of C1q and C3 correlated inversely with sHLA-I concentration. In five serial samples from ten patients the sHLA-I level co-varied with disease activity. Presence of HLA allotype A9 was associated with higher sHLA-I levels in both patients (P< 0.001) and controls (P< 0.001). We conclude that the increased sHLA-I concentration in SLE patients was related to several laboratory parameters reflecting disease activity suggesting that sHLA-I molecules are connected with the disease process. Increased sHLA-I level due to HLA-A allotype was not a disease susceptibility factor for SLE.

Adult↗
PubMed1990

Immunohistologic findings in otosclerosis.

The cause of otosclerosis is still unclear. Between 1981 and 1988 we obtained 186 biopsy specimens of otosclerotic bone during the course of stapedectomies. Serial sections of the specimens were examined histologically (H & E) and immunohistologically (peroxidase-antiperoxidase technique) for immunoglobulin G, immunoglobulin M, and C1q and C3 complements. Active otosclerotic foci were found in 61 cases, 43 of which had IgG deposits. IgM antibodies were absent. In specimens with inactive otosclerosis, IgG and IgM were not evident, C1q and C3 complements were demonstrated together with IgG, but sometimes also in the mucosa independent of the phase of the otosclerosis. Our findings suggest that an immunologic process may be important in the pathogenesis of otosclerosis.

Acute Disease↗
PubMed1985

Effect of ascorbic acid nutriture on protein-bound hydroxyproline in guinea pig plasma.

This paper provides indirect evidence that ascorbate nutriture affects plasma concentrations of complement component C1q in the guinea pig. C1q is a protein with a hydroxyproline-rich region similar in structure to collagen. It is essential for complement-mediated lysis of pathogens and may also facilitate phagocytic activity of macrophages and neutrophils. Since C1q is the only hydroxyproline-containing protein in the euglobulin fraction of plasma, it can be quantified indirectly by precipitating this fraction, hydrolyzing it and estimating hydroxyproline colorimetrically. We investigated the effect of ascorbate nutriture on protein-bound hydroxyproline (PBH) in the euglobulin fraction of plasma of young male guinea pigs. The animals had been depleted of ascorbate for 3 wk to produce scurvy and then repleted (6 wk) as follows: 0.5, 2.0 and 10.0 mg ascorbate/100 g body weight per d or 10 g ascorbate per liter of drinking water. PBH values were significantly correlated (P less than 0.001) with dietary ascorbate (+ 0.74) and with liver ascorbate (+ 0.75). Plasma PBH was significantly higher (P less than 0.01, Scheffé's test) in guinea pigs fed ample ascorbate (10.0 mg/100 g body weight per day) or tissue-saturating levels (10 g/L of drinking water) than in those fed adequate (2.0 mg/100 g body weight) or suboptimal (0.5 mg/100 g body weight) levels. These data are consistent with the known biochemical role of ascorbic acid in hydroxyproline biosynthesis and suggest a possible link between ascorbate and the immune response via C1q.

Animals↗
PubMed1989

Immune complexes and rheumatoid factors in canine arthritides.

Thirty two domestic dogs with naturally occurring polyarthritis were investigated to determine the contribution of autoimmunity in the pathological mechanisms. Comparisons were made with canine infective arthritis (12 dogs), osteoarthritis (32), and osteoarthritis secondary to rupture of the cranial cruciate ligament (19). Rheumatoid factors, immune complexes, and complement fixation (C1q binding) were measured in sera and synovial fluids. Compared with normal dogs (32), dogs with rheumatoid arthritis (RA) had increased serum and synovial fluid immune complexes and rheumatoid factors. Increases were generally also seen in dogs with other arthropathies, however. Rheumatoid factors were higher in sera than in synovial fluids. Rheumatoid factors correlated with immune complex levels and complexed rheumatoid factor only in the group of dogs with RA. Both rheumatoid factors and immune complexes may contribute to the pathogenesis of canine RA but are considered to arise as a result of non-specific inflammatory mechanisms in the non-rheumatoid groups.

Animals↗
PubMed1983

Circulating immune complexes in patients with diabetes mellitus.

Circulating immune complexes (CIC) were detected by the solid phase C1q binding assay in 16% of 103 diabetic patients and by the fluid phase C1q binding assay in 31% of patients as compared to 5% of 58 control subjects for each assay. Plasma glucose determinations revealed that most patients were moderately hyperglycaemic (mean glucose = 264 mg/dl), and thus were not selected for tight metabolic control. All but six patients had elevated levels of plasma insulin, including both the insulin treated and diet treated subgroups. There was no correlation between the presence of CIC detected by either assay and plasma glucose, insulin, or the presence of microangiopathy. Multiple factors must contribute to the increase in CIC in both insulin deficient and insulin resistant diabetics. The role of these various factors remains to be defined.

Adult↗
PubMed2005

Predominant tubulointerstitial nephritis in a patient with systemic lupus nephritis.

In most cases of systemic lupus erythematosus (SLE), glomerular lesions are the main renal complication. Although tubulointerstitial lesions are often associated with severe glomerular lesions, predominant or isolated tubulointerstitial injury in the presence of minimal glomerular abnormalities with SLE, so-called predominant tubulointerstitial lupus nephritis, is rare. Only ten cases are reported in the English literature. Herein, we describe the case of a 64-year-old man with SLE who presented with acute renal deterioration attributable to acute tubulointerstitial nephritis. Renal biopsy showed diffuse infiltration of inflammatory mononuclear cells in the interstitium and tubulitis without significant glomerular lesions. Immunofluorescence study revealed positive staining for IgG, C3, and C1q along the renal tubular basement membrane (TBM). Electron microscopy also showed electron-dense deposits in the TBM. Other causes of tubulointerstitial injury, such as drug use and infection, were ruled out. Taking these findings together with the presence of antitubular basement membrane antibody, predominant tubulointerstitial lupus nephritis was diagnosed. Treatment with oral corticosteroids for 6 weeks improved renal function. Even after tapering of the corticosteroid, renal function and serological markers of SLE activity have remained stable in this patient for more than 12 months.

Administration, Oral↗
PubMedDate not supplied

Significance of circulating C1q-binding activity in chronic liver disease: a study of 133 cases.

Circulating immune complexes (CIC) were measured in 133 biopsy-proven patients with various liver diseases. The correlation between CIC levels and other laboratory findings was investigated in each disease group, in order to assess if the increased C1q-binding activity found in these patients was related to particular features of the disease. CIC levels were not significantly different in HBsAg-positive and HBsAg-negative patients. No correlation was found between CIC levels and serum bilirubin, AST, ALT and C3 levels. A negative correlation with C4 levels and a positive correlation with immunoglobulin levels were found in the majority of the patients, while prothrombin time and albumin levels were negatively correlated to CIC levels only in patients with chronic active hepatitis. Increased CIC levels could represent a response to gut-associated antigens, a passive accumulation due to reduced hepatic function or both.

Alanine Transaminase↗
PubMed1996

The formation of insoluble immune complexes between ovalbumin and anti-ovalbumin IgG occurs in at least two distinct phases dependent on reactant concentration and ionic strength.

The mechanism regulating the formation of insoluble immune complexes (IIC) in serum in certain disease states is not well understood. Ovalbumin and rabbit anti-ovalbumin IgG was used to study the formation of IIC in vitro in a stirred reaction vessel; and the radii of IIC that formed was determined by light scattering techniques. Using an initial IgG concentration of 1 mg/ml at equivalence antigen:antibody ratio IIC formation was detected within 5 s, and the complexes increased in radii to approx. 100 nm after 20-30 s (phase 1). This was followed by a phase (phase 2) in which the complexes rapidly increased in radii to the point where Mie scattering was reached (approximately 200 nm). The time of onset of the second phase decreased with increasing initial IgG concentrations at a fixed antigen:antibody ratio; and was at a minimum at equivalence antigen:antibody ratio, but increased at both antigen and antibody excess ratios. Immune complexes formed using F(ab')2 fragment showed a similar pattern to those formed using IgG. A similar pattern was seen in the presence of the complement component C1q which potentiated IIC formation in phase 2, and human serum (1:10 dilution) which attenuated IIC formation in both phases. For complex formation using IgG and ovalbumin the presence of NaC1 at concentrations up to 0.6 M led to a progressive increase in the time of onset of phase 2; potencies of inhibition by other sodium halides followed the lyotropic series NaF < NaC1 < NaI. The results suggest that formation of IIC occurs in at least two distinct phases, and that the second phase leading to the generation of very large insoluble complexes is associated with a rapid polymerisation of the complexes by a mechanism that is not dependent on Fc:Fc interactions.

Animals↗
PubMed1999

Immunogenicity of peptides derived from a fibronectin-binding protein of S. aureus expressed on two different plant viruses.

The D2 peptide derived from an S. aureus fibronectin-binding protein (FnBP) was expressed on the surface of the icosahedral cowpea mosaic virus (amino acids 1-30 of D2) or on the rod-shaped potato virus X (amino acids 1-38 of D2), termed CPMV-MAST1 and PVX-MAST8, respectively. Mice and rats were immunized subcutaneously with CPMV-MAST1 and mice with PVX-MAST8 in adjuvant and high titres of FnBP-specific antibody were obtained. The mouse IgG was predominantly of the IgG2a and IgG2b isotypes, which strongly bound complement component C1q, suggesting a TH1-bias in the peptide-specific responses. Sera from mice and rats immunized with CPMV-MAST1 and from mice immunized with PVX-MAST8 were shown to completely inhibit the binding of fibronectin to immobilised recombinant FnBP and rat sera against CPMV-MAST1 were able to block adherence of S. aureus to fibronectin. These studies demonstrate that the D2 peptide is highly immunogenic when expressed on 2 different plant viruses and highlight the potential of plant virus-based vaccines to protect against S. aureus infections.

Adhesins, Bacterial↗
PubMed1983

Interference of IgG, IgG aggregates and immune complexes in tests for platelet autoantibodies.

Three techniques, based on the antiglobulin principle, used for the detection of autoantibodies against platelets, were compared; the antiglobulin consumption assay (QACA), the platelet radioactive antiglobulin test (PRAT) and the platelet suspension immunofluorescence test (PSIFT). Upon incubation of normal donor platelets with purified IgG, in concentrations higher than that in serum, an increased amount of platelet-associated IgG was demonstrated only in the QACA. Upon incubation with aggregated IgG, all three tests became positive, but the PSIFT only with high concentrations of aggregates. Binding of soluble C1q-binding immune complexes (IC), which consisted of tetanus toxoid and IgG antitetanus antibodies (TaT) to normal donor platelets, was only detectable in the QACA. However, a positive result was obtained in all three tests with platelets incubated with soluble DNA-IgG-antiDNA antibodies (DaD) IC. Fixation of the platelets with paraformaldehyde prevented the binding and the detection of the DaD-IC, but not of IgG, aggregated IgG or TaT-IC. Eluates from platelets incubated with aggregated IgG, TaT- or DaD-IC did not react with normal donor platelets in the three techniques, in contrast to eluates from platelets sensitized with platelet antibodies.

Antibodies, Antinuclear↗
PubMed2001

Comparative study of circulating immune complexes quantity detection by three assays--CIF-ELISA, C1q-ELISA and anti-C3 ELISA.

The assessment of the soluble immune complexes (IC) in human sera is traditionally performed by the C1q binding assay. In the present study, a novel method for the quantity of immune complexes was reported. The methodology was based on measuring their deposition on solid-phase C3 binding glycoprotein (CIF), using an enzyme-linked immunosorbent assay. We also used ELISA that employed anti-C3 antibodies to determined the quantity of immune complexes. The three assays were evaluated for their performance characteristics on the same specially prepared samples: 55 normal sera, 99 sera from RA, 88 sera from SLE, and 27 sera from PSS. The results were compared by reference to a common standard-heat aggregated IgG that possesses many activities of immune complexes. Three of the tests used displayed almost the same specificity (over 95%), while their relative sensitivity varied depending on the disease sera tested. The sensitivity of the assays used was recorded highest for C1q ELISA-28.97% of positive sera, followed by CIF-ELISA-19.63% and lowest for anti-C3 ELISA-17.29%. A well-expressed correlation was found between CIF-ELISA and anti-C3 ELISA data (r=0.42), and a week correlation was noted when comparing CIF-ELISA and C1q ELISA IC levels detected (r=0.28). When the correlation coefficients were calculated individually for each disease category, they were clearly different, and that reflected indirectly in different sensitivities of the test for various disease categories. We also found that the results from the simultaneous performance of the tests demonstrated low percentage positive results when three or two assays were used. This is most probably due to the different assay abilities to detect IC with different sizes and composition, which shows that a small part of IC in the tested sera can be detected simultaneously by more than one assay. On the basis of the results obtained, we concluded that optimal screening for IC could be achieved by parallel application of several different methods.

Antibodies↗
PubMed2000

Renal immunofluorescence and the prediction of renal outcome in patients with proliferative lupus nephritis.

The risk for endstage renal failure in patients with proliferative lupus nephritis (PLN) depends largely on the severity and reversibility of the inflammatory process as determined by light microscopy (LM). As the intrarenal formation of immune complexes is thought to initiate this inflammation, we studied whether renal immunofluorescence microscopy (IFM) provides clinical or prognostic information in addition to LM findings. Clinical data at the time of renal biopsy and during a mean follow-up of 46 months were extracted from the records of 69 SLE patients with proliferative LN (WHO class III/IV). Biopsy specimens were analyzed by LM for AI and CI, while IFM was performed on cryostat sections with the use of antisera against IgG, IgM, IgA, C3, C1q and fibrin. IFM findings were recorded in terms of the localization (glomerular, tubular or vascular) and intensity of fluorescence (score from zero to three). IFM findings were then related to clinical and LM findings and its prognostic value studied by survival analysis. Glomerular immune deposits were present in 99% of patients, tubular deposits in 38% and vascular deposits in 17%. A 'full-house' pattern (all three Ig classes) was found in 67% of biopsies and C3 and C1q deposits in 93% and 74% respectively. Median scores for AI and CI were 6 (1-18) and 3 (0-10); aside from a negative correlation between IgA deposits and CI, we found no other correlation between the amount or type of immune deposits and AI or CI. IgM deposits were associated with high serum levels of anti-dsDNA, while IgG deposits correlated with high ESR and serum creatinin levels. IFM scores were not related to steroid dose at the time of biopsy and neither type of glomerular, tubular or overall renal immune deposits had prognostic value for renal survival. Renal immunofluorescence does not reflect light microscopy findings in patients with PLN and does not contribute prognostic information in patients with PLN. Lupus (2000) 9, 504-510.

Adolescent↗
PubMed1991

Human follicular dendritic cells: isolation and characteristics in situ and in suspension.

Follicular dendritic cells (FDC) in human tonsils, either in situ in follicular germinal centres or isolated from tissue, were characterized by immunohistochemical, enzyme cytochemical and electron microscopical methods. Using polyclonal and monoclonal antibodies, expression of DRC-1, Ki-M4, HLA-DR, CR1, C1q antigens, a macrophage marker, and surface IgG and IgM were found on isolated FDC and on FDC in situ. None of these reagents proved to be specific for FDC, e.g. the FDC-directed antibodies DRC-1 and Ki-M4 labelled B lymphocytes in cytofluorography. Enzyme cytochemical staining revealed activities of non-specific esterase, acid alpha-naphthylacetate esterase and ATPase in germinal centres and in freshly isolated FDC. Immunohistochemistry demonstrated a weak expression of CD4 by a fraction of isolated FDC, which was confirmed by two-colour immuno-staining and immuno-electron microscopy.

5'-Nucleotidase↗
PubMed1993

Autoimmune C1 inhibitor deficiency: report of eight patients.

PURPOSE: In this study, we investigated the clinical and biochemical features and the responses to treatment of eight patients with auto-antibody-mediated C1 inhibitor (C1-INH) deficiency and symptoms of angioedema. PATIENTS AND METHODS: In addition to the 8 patients with acquired angioedema (AAE), we also studied 36 subjects with hereditary angioedema (HAE), 15 of them treated with C1-INH plasma concentrate, and 26 patients with different autoantibodies in their plasma (10 with systemic lupus erythematosus, 6 with lupus-like anticoagulant, and 10 with chronic liver disease). Functional C1-INH was measured with the reagent kit of Immuno (Vienna, Austria); C1-INH, C4, and C1q antigen were determined by radial immunodiffusion; and autoantibodies to C1-INH were detected by an enzyme-linked immunosorbent assay method. RESULTS: Four patients with AAE had no other diseases, one had breast cancer, one liver hydatidosis, one Waldenström's disease, and one a benign M component. Functional C1-INH levels were below 30% of normal, and C1q plasma levels were low in seven patients but normal in one. Autoantibodies to C1-INH were detectable in all eight AAE patients but in none of the others. Prophylactic treatment with attenuated androgens was successful in one of four patients, and with antifibrinolytic agents (tranexamic acid) in six of seven patients. Laryngeal attacks in five patients were treated with C1-INH plasma concentrate; two patients had marked clinical and biochemical responses. In three, the symptoms resolved only with high doses, and the biochemical parameters did not significantly increase. CONCLUSIONS: Our results suggest that patients with autoimmune AAE are clinically and biochemically heterogeneous. They have different responses to treatment that seem to be related to variable C1-INH consumption.

Aged↗
PubMed1985

Circulating immune complexes and rheumatoid arthritis: a comparison of different assay methods and their early predictive value for disease activity and outcome.

The performance of four different assays for circulating immune complexes-the C1q solid phase method, one using protein A and one using anti-IgG, C1q PEG, and the 2% PEG method-were compared in 61 patients with early rheumatoid arthritis followed up for two years. There were weak but statistically significant correlations between the results from some of the pairs of assays, but the changes over time from any single assay did not correlate with those from any of the other assays. None of the assays predicted either future disease activity, as measured by subsequent ESR, CRP, and articular index; or functional outcome, as measured by wrist extension, Steinbocker functional capacity, and the Stanford health assessment questionnaire. It is unlikely therefore that the measurement of immune complexes is of value in predicting early outcome in patients with rheumatoid arthritis.

Adult↗
PubMed1993

Regulation of the synthesis of C1 subcomponents and C1-inhibitor.

We have investigated the synthesis of C1q, C1r, C1s and C1-inhibitor in HepG2 cells, human umbilical vein endothelial cells (HUVEC), fibroblasts (skin and synovial membrane), chondrocytes and monocytes. C1q was only synthesised by monocytes, although the mRNAs for the C1qA and C1qC chains were expressed in HUVEC. C1r, C1s and C1-inhibitor were synthesised by all cell types. The secretion rates of C1r and C1s were approximately equimolar in fibroblasts and chondrocytes whereas the secretion rate for C1s exceeded that for C1r in the other cell types. Molar ratios of C1s to C1r were approximately 2:1 for HepG2 cells, 5:1 for monocytes and 10:1 for HUVEC. Stimulation with interferon-gamma resulted in increased expression of all four proteins. The C1s:C1r ratio did not alter in chondrocytes or fibroblasts, but approached unity in HepG2, monocytes and HUVEC, due to relatively greater stimulation of C1r gene expression.

Carcinoma, Hepatocellular↗